The principal goal of the proposed research program is to provide a better understanding of hemoglobin synthesis in the thalassemia syndromes, the hemoglobinopathies, and in normal red cells. The studies will include an investigation of these in a variety of unusual forms of thalassemia, the mechanism of the control of balanced globin synthesis in normal cells, the interaction between globin and the red cell membrane, and abnormalities in sickle cell anemia and the unstable hemoglobin syndromes. These studies will utilize data from hematologic, genetic and biochemical analysis of individual patients and families in order to obtain a better understanding of the hemoglobinopathies. The long range objective of these studies is to provide new information which will be of benefit to patients with hemoglobin disorders.